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apo-8,6' 胡萝卜素与完整番茄红素对乳腺癌细胞间通讯增强和细胞凋亡诱导机制的化学影响。

Chemical Implications of apo-8, 6' Carotendial versus Intact Lycopene on Mechanism of Enhanced Cell-cell Communication and Apoptosis Induction in Breast Cancer Cells.

机构信息

Department of Microbiology and Biotechnology, Jnana Bharathi Campus, Bangalore University, Bengaluru, 560 056, India.

Department of Biochemistry, Indian Institute of Science, Bengaluru, 560 012, India.

出版信息

Cell Biochem Biophys. 2024 Dec;82(4):3517-3533. doi: 10.1007/s12013-024-01440-4. Epub 2024 Jul 31.

Abstract

Investigation on carotenoids and its cleavage products is crucial to combat the development of chronic diseases, including cancer. Therefore, this study aimed to explore the effect of lycopene oxidative products versus equivalent concentration of lycopene (LYC) on major molecular events of cancer cells (MCF-7). Primarily, LYC-oxidized products were generated chemically, then collected its rich fraction. Based on cell-based assays, the antiproliferation potency of rich fraction of chemically-oxidized lycopene (COL) identified as apo-8, 6' carotendial was compared with LYC. Interestingly, the inhibition of cell migration by COL strongly demonstrated anti-metastatic activity. Further, the increased connexin-43 expression confirms enhanced gap-junctional communication activity of COL than LYC and control. Fortunately, apo-8, 6' carotendial did not affect normal breast epithelial cells. We anticipated that, the chemical properties of apo-8, 6'-carotendial is similar and mimic a model compound acrolein (α, β-conjugated aldehyde) which is involved in Michael addition/Schiff base formation with specific amino acids and regulates redox signaling, reactive oxygen species sensing and cellular buffering. The chemistry of apo-8, 6' carotendial reveals a greater insight into the mechanism of selective inhibition of cancer cells proliferation. In this context, speculations of putative action of lycopeneoids through chemical biology approach facilitate greater insights in tandem with synthetic chemistry.

摘要

对类胡萝卜素及其裂解产物的研究对于防治包括癌症在内的慢性疾病的发展至关重要。因此,本研究旨在探讨番茄红素氧化产物与等效浓度的番茄红素(LYC)对癌细胞(MCF-7)主要分子事件的影响。首先,通过化学方法生成 LYC 氧化产物,然后收集其富含的部分。基于细胞试验,比较了富含化学氧化番茄红素(COL)的类胡萝卜素-apc-8,6'-carotendial 的增殖抑制作用与 LYC。有趣的是,COL 对细胞迁移的抑制作用强烈证明了其具有抗转移活性。此外,连接蛋白-43 的表达增加证实了 COL 比 LYC 和对照具有增强的间隙连接通讯活性。幸运的是,apo-8,6'-carotendial 不会影响正常的乳腺上皮细胞。我们预计,apo-8,6'-carotendial 的化学性质相似,并模拟了一种模型化合物丙烯醛(α,β-共轭醛),它参与与特定氨基酸的迈克尔加成/席夫碱形成,并调节氧化还原信号、活性氧感应和细胞缓冲。apo-8,6' carotendial 的化学性质揭示了对癌细胞增殖选择性抑制的机制的更深入了解。在这种情况下,通过化学生物学方法推测番茄红素类化合物的可能作用与合成化学相结合,有助于更深入的了解。

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